DURHAM, N.C. -- In findings that can not totally be explained but are sure to lead to future research, Duke Clinical Research Institute investigators have found that adherence to medical therapy, even if the medication is an inert placebo, relates to better outcomes for heart failure patients.

This finding persisted even after the researchers statistically controlled for a wide variety of patient and treatment characteristics. The researchers also said that their findings do not appear to be a statistical quirk because of the large numbers of patients involved and the length of follow-up in the clinical trial that served as the basis for their analysis.

In an international clinical trial of 7,599 heart failure patients, the researchers found that good adherence was associated with similar lower mortality rates for both the placebo and an angiotensin receptor blocker (ARB), a medication used to relax and dilate blood vessels, when compared to patients who were not as adherent. Also, good adherence was associated with lower rates of hospitalization for both placebo and active drug.

"Adherence to medications is one of the most important predictors of clinical outcomes for patients with complex diseases like heart failure," said Bradi Granger, Ph.D., who presented the results of the Duke analysis Nov. 9, 2004, at the American Heart Association's annual scientific sessions in New Orleans.

"Our finding that adherence to a placebo was an important and independent predictor of better outcomes suggests that adherence itself is a marker for other unmeasured variables that can determine outcome," Granger continued. "Understanding these factors may provide an opportunity for novel interventions, including those targeted at improving adherence."

Also known as congestive heart failure, heart failure is a condition characterized by the thickening of the walls of the heart. Over time this thickening restricts the heart's ability to pump enough blood to the body's tissues, and thereby to provide them with oxygen and nutrients. The typical heart failure patient takes an average of six different medications to control their symptoms and improve their quality of life, the researchers said.

An estimated 5 million Americans suffer from the condition, with 400,000 new cases reported each year. Half of the patients die within five years of the diagnosis, typically after repeated hospitalizations.

According to Granger, about two-thirds of all hospital admissions for heart failure are preventable and due to non-compliance in such areas as diet, close attention to symptoms and adherence to drug regimens. Since it has been known that poor adherence can limit the effectiveness of medications for heart failure patients, the researchers studied the issue in a large double-blind, randomized controlled clinical trial of the ARB candesartan.

The five year trial, Candesartan in Heart Failure Assessment of Mortality and Morbidity (CHARM), was one of the largest such trials and had an average patient follow-up of 38 months. Adherence was measured as the proportion of time patients took at least 80 percent of the study medication.

Two earlier heart studies – the Coronary Drug Project in 1980 Beta-Blockers in Heart Attack in 1982 – showed similar patterns as the new Duke analysis, and according to Granger, researchers have attempted over the years without success to in explain the beneficial effects of adherence in those studies. Researchers have studied such non-medical variables as martial status, stress, education and social isolation, but could not uncover a statistical link to adherence, she said.

"The consensus is that there must be something that differentiates people who adhere from people who do not," Granger said. "We don't know why, but they are different in terms of outcome."

Even without an understanding of the reasons for this phenomenon, Granger does believe that improving adherence should help patients avoid frequent hospitalization and improve survival. Such strategies as calling or mailing reminders to patients about taking their medications, involving friends or family members their care, or simplifying the drug regimen have been shown to improve compliance, Granger said.

"These strategies can be effective, but they are expensive and labor-intensive," Granger said. "It would be helpful if we could determine what characteristics predict non-adherence, and so could target our efforts toward that population of patients."

The CHARM trial was funded by AstraZeneca, Mondal, Sweden. Granger's analysis was supported by the Duke Clinical Research Institute.